Mammalian target of rapamycin (mTOR) inhibition as a potential antiepileptogenic therapy: from tuberous sclerosis to common acquired epilepsies.
Open accessAbstract
Most current treatments for epilepsy are symptomatic therapies that suppress seizures but do not affect the underlying course or prognosis of epilepsy. The need for disease-modifying or "antiepileptogenic" treatments for epilepsy is widely recognized, but no such preventive therapies have yet been established for clinical use. A rational strategy for preventing epilepsy is to target primary signaling pathways that initially trigger the numerous downstream mechanisms mediating epileptogenesis. The mammalian target of rapamycin (mTOR) pathway represents a logical candidate, because mTOR regulates multiple cellular functions that may contribute to epileptogenesis, including protein synthesis, cell growth and proliferation, and synaptic plasticity. The importance of the mTOR pathway in epileptogenesis is best illustrated by tuberous sclerosis complex (TSC), one of the most common genetic causes of epilepsy. In mouse models of TSC, mTOR inhibitors prevent the development of epilepsy and underlying brain abnormalities associated with epileptogenesis. Accumulating evidence suggests that mTOR also participates in epileptogenesis due to a variety of other causes, including focal cortical dysplasia and acquired brain injuries, such as in animal models following status epilepticus or traumatic brain injury. Therefore, mTOR inhibition may represent a potential antiepileptogenic therapy for diverse types of epilepsy, including both genetic and acquired epilepsies.
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The mammalian target of rapamycin is a highly conserved protein kinase implicated in cell survival, growth, proliferation, migration, and differentiation.
“The mammalian target of rapamycin (mTOR) is a highly conserved protein kinase that is implicated in a wide array of cellular and metabolic functions, including cell survival, growth, proliferation, migration, and differentiation (Wong, 2010; Mueed et al., 2018).”
From Tauopathy and Epilepsy Comorbidities and Underlying Mechanisms (2022) · cites this paper as Wong, 2010
The section “mTOR: A Central Regulator of Cell Growth, Proliferation & Survival” describes mTOR as a highly conserved protein kinase involved in growth, proliferation, metabolism, and survival. Our copy does not establish cell migration or differentiation as mTOR functions; the only direct migration hit is in a cited work’s title in the references. Page numbers were not available in the indexed passages. (LLM, conf=0.88)
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“The mammalian target of rapamycin (mTOR) is a highly conserved protein kinase that is implicated in a wide array of cellular and metabolic functions, including cell survival, growth, proliferation, migration, and differentiation (Wong, 2010; Mueed et al., 2018).”
Background
- Authors
- Wong, M.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Wong, Michael
- ORCID
- Wong, Michael
- Venue
- Epilepsia
- Publisher
- Wiley
- Published
- 2009-12-21
- Volume
- 51
- Issue
- 1
- Pages
- 27-36
- ISSN
- 0013-9580 (ISSN-L)
- 1528-1167
- PMC
- PMC3022513
- OpenAlex
- W2019723714
- Cited by
- 205
- References
- 12
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 6 · 2023: 6 · 2022: 7 · 2021: 8 · 2020: 10 · 2019: 10 · 2018: 9 · 2017: 11 · 2016: 11 · 2015: 12 · 2014: 19 · 2013: 23 · 2012: 35
- FWCI
- 14.02
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Epilepsia (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Citizens United for Research in Epilepsy
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (K02NS045583, R01NS056872)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Health Sciences › Medicine › Physiology › Tuberous Sclerosis Complex Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- mTOR inhibition, antiepileptogenic therapy, epileptogenesis, tuberous sclerosis complex, acquired epilepsy, focal cortical dysplasia, status epilepticus, traumatic brain injury, synaptic plasticity
- MeSH terms
- Animals, Anticonvulsants, Brain Injuries, Cell Division, Disease Models, Animal, Epilepsy, Gene Expression Regulation, Humans, Models, Genetic, Neuronal Plasticity, Tuberous Sclerosis, Signal Transduction, Cell Death, Protein Serine-Threonine Kinases, Sirolimus, Ribosomal Protein S6 Kinases, 70-kDa, Intracellular Signaling Peptides and Proteins, Cell Proliferation, Mice, Malformations of Cortical Development, TOR Serine-Threonine Kinases
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